Journal of the Neurological Sciences 341 (2014) 165–166

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Journal of the Neurological Sciences

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Short communication

Opsoclonus–myoclonus syndrome associated with human herpesvirus-6 rhomboencephalitis

Vincenzo Belcastro a,⁎, Mirko Piola a, Sandro Binda b, Domenico Santoro c,Monica Rezzonico a, Marco Arnaboldi a

a Neurology Unit, Department of Medicine, S. Anna Hospital, Como, Italyb Department of Biomedical Sciences for Health, University of Milan, Milan, Italyc Department of Medicine, S. Anna Hospital, Como, Italy

⁎ Corresponding author at: Neurology Unit, Departmenvia Ravona, 22100 Como, Italy. Tel.: +39 0 31 5859682; f

E-mail address: vincenzobelcastro@libero.it (V. Belcas

http://dx.doi.org/10.1016/j.jns.2014.04.0130022-510X/© 2014 Elsevier B.V. All rights reserved.

a b s t r a c t

a r t i c l e i n f o

Article history:Received 9 March 2014Received in revised form 7 April 2014Accepted 9 April 2014Available online 18 April 2014

Keywords:Opsoclonus–myoclonus syndromeHuman herpes virus-6 infectionRhomboencephalitis

Opsoclonus–myoclonus syndrome (OMS) is characterized by opsoclonus and arrhythmic-action myoclonus thatpredominantly involves the trunk, limbs, and head. Human herpes virus-6 (HHV-6) can rarely cause encephalitisin immunocompetent children and adults. Here we report on a case of OMS associated with HHV-6rhomboencephalitis. HHV-6 infection should be considered in OMS adults and detection of cell-free viral DNA,indicative of active infection, is mandatory in such cases.

© 2014 Elsevier B.V. All rights reserved.

1. Introduction

1.1. Case report

A 63-year-old man presented with balance difficulties, nausea andvision abnormalities.

At admission, the patient showedbursts of high-frequency, conjugateocular oscillationswith horizontal, vertical, and torsional components, allof which indicated opsoclonus. “Tremor-like” head movements werealso observed, suggestive of opsoclonus–myoclonus syndrome (OMS)(Video 1). Moreover, cerebellar ataxia and arrhythmic-actionmyoclonusthat predominantly involves the trunk and the arms were also present.Screen for autoimmune disease, malignancy and paraneoplastic anti-bodies (anti-amphiphysin, anti-Ri, anti-Yo, anti-Hu) as well as MRI ofthe brain were unremarkable. Cerebrospinal fluid (CSF) analysis re-vealed pleocytosis (93 WBCs/mm3) and elevated protein (158 mg/dL).A viral rhomboencephalitis was suspected on the basis of the patient'sclinical presentation andCSFfindings, andantiviral therapywith intrave-nous acyclovir (12.5 mg/kg every 8 h) was started. The patient firstreceived 14-day intravenous acyclovir with poor recovery. Myoclonuswas managed with clonazepam and sodium valproate. Despite treat-ment there was no notable improvement over a 3-week period whileinvestigation was ongoing.

t of Medicine, S. Anna Hospital,ax: +39 0 31 5859684.tro).

Noteworthy, human herpes virus-6 (HHV-6) was detected in bothCSF and blood specimens by using a nested polymerase chain reaction(PCR) assay amplifying a fragment (258 nt.) of the gene encoding forthemajor capsid protein [1]. HHV-6 DNAwas then quantified by a com-mercial real time-PCR assay (CMVHHV6,7,8 R-gene™ quantification kit,Argene), which amplifies a region of the U57 gene. HHV-6 DNA concen-tration was 2959.5 copies/mL in CSF and 9.83 × 106 in blood. HHV-6-positive samples were also subtyped by sequence analysis of viralgene encoding for the immediate early protein and the virus demon-strated homology to the B (HST) variant. Notable, herpes viruses (HSV1-2, CMV, EBV, VZV), HIV, JCV,West Nile virus, fleboviruses, and entero-viruses were excluded. Thus, we gave the patient ganciclovir (5 mg/kgevery 12 h) for two weeks with remarkable recovery. At the last neuro-logical assessment, the patientwas able towalk and the eyemovementswere normal (Video 2).

2. Discussion

OMS is characterized by opsoclonus and arrhythmic-action myoclo-nus that predominantly involves the trunk, limbs, and head. The syn-drome is associated with multiple aetiologies, most commonly infectionandunderlying neoplasm [2]. In adult onset OMS, paraneoplastic etiologyis relatively rare with most patient having presumable parainfectiouscause [2].

HHV-6 is one of the more recently identified herpes viruses and itcan rarely cause encephalitis in immunocompetent children and adults

166 V. Belcastro et al. / Journal of the Neurological Sciences 341 (2014) 165–166

[3]. Noteworthy, HHV-6 infections are benign and self-limited illnesses,although the virus appears to be the major cause of the syndrome ofpost-transplant acute limbic encephalitis [3]. Most adults have been in-fected with HHV-6 in the childhood and virus then persists for life in alatent form in blood and vascular endothelial cells. HHV-6 can reactivatetypically in immunocompromised individuals and reactivation canoccur after stem cell or bone marrow transplant, pregnancy, hypersen-sitivity syndromes, critical illness, and acute infectionwith other viruses(measles, influenza, dengue) [4]. Notably, our patientwas not immuno-compromised and other neurotropic viruses were excluded.

The diagnosis of HHV-6 infection is a complex issue and mostwidely used diagnostic tests for HHV-6 are unable to distinguishbetween latent and active forms of infection. However, the detectionby PCR of HHV-6 DNA in both CSF and blood, indicative of active viralreplication [1,3], the clinical improvement after ganciclovir treat-ment [5] and a negative paraneoplastic screen strongly suggest thatthe patient's OMS was caused by HHV-6 infection. Of note, ganciclo-vir is superior to acyclovir for HHV-6 but it treats only lytic phase in-fection [5].

The lifetime consequences of infection with HHV-6 are not wellknown and the follow-up of our patient is still ongoing. OMS associatedwith HHV-6 infection has not previously been reported in immunocom-petent adults. In our patient, the precise mechanism of how HHV-6 in-fection resulted in rhomboencephalitis still remains to be defined.

Interactions between host immunity and CNS glial cells after exposureto herpesviruses could contribute to neuropathology of OMS [3].

HHV-6 infection should be considered in OMS adults and detectionof cell-free viral DNA, indicative of active infection, is mandatory insuch cases [3].

Supplementary data to this article can be found online at http://dx.doi.org/10.1016/j.jns.2014.04.013.

Conflict of interest

All authors report no disclosures.

References

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[2] Klaas JP, Ahlskog JE, Pittock SJ, Matsumoto JY, Aksamit AJ, Bartleson JD, et al. Adult-onset opsoclonus–myoclonus syndrome. Arch Neurol 2012;69:1598–607.

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